title: αTAT1 catalyses microtubule acetylation at clathrin-coated pits.
abstract: In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge, and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis.
authors.affiliation: 1] Institut Curie, Research Center, 75005 Paris, France [2] Membrane and Cytoskeleton Dynamics, CNRS UMR 144, 75005 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Montagnac
authors.forename: Vannary
authors.initials: V
authors.lastname: Meas-Yedid
authors.forename: Marie
authors.initials: M
authors.lastname: Irondelle
authors.forename: Antonio
authors.initials: A
authors.lastname: Castro-Castro
authors.forename: Michel
authors.initials: M
authors.lastname: Franco
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Shida
authors.forename: Maxence V
authors.initials: MV
authors.lastname: Nachury
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benmerah
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavrier
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D055162:Biocatalysis; D002465:Cell Movement; D002966:Clathrin / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000201:enzymology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism
chemical_list: D033962:Adaptor Protein Complex 2; D002966:Clathrin; D014404:Tubulin; D000123:Acetyltransferases; C049182:alpha-tubulin acetylase